Age at menopause has been proposed as a marker of aging and health. Several studies, including one we published using data from the National Health and Examination Survey (NHANES) Epidemiologic Follow-up Study reported increased mortality risk with early natural menopause. Another recent study reported reduced mortality risk among women who gave birth at ages 40 years. We examined the association between reproductive history and mortality in a prospective study involving 18,959 person-years of follow-up and 108 deaths among 826 women. Among parous women, the age- and other covariate-adjusted risk ratio (RR) was 1.5 (95% confidence interval (CI) 0.6 4.1) for natural menopause at ages 45 years compared with 51 years. In contrast to the previous report, however, the highest estimated mortality risk was seen in women with a birth in their 40s (adjusted RR 2.1, 95% CI 1.1 4.4) compared with last birth between ages 30 34 years). We also used data from this study to examine smoking in relation to natural menopause in 543 women who prospectively recorded menstrual data from their 20s through their menopause. Mean age at natural menopause was 0.8 years younger (95% CI 1.5, 0.0) in 98 women who smoked at menopause compared with 362 never- smokers (RR 1.3, 95% CI 1.0 1.7). We did not observe a decrease in age at natural menopause in former smokers, a dose-response among current smokers, or a lower age at menopause with passive smoke exposure at home. These results suggest that the effect of smoking on ovarian senescence is limited to active smoking during the menopausal transition. The National Health and Nutrition Examination Survey (NHANES) III, conducted from 1988-1994 provides an opportunity to examine specific medical and behavioral risk factors for early menopause. We examined correlates of follicle-stimulating hormone (FSH), a gonadotropin that can be used as a measure of menopausal status in a sample of 1716 women ages 35 to 49 in the NHANES-III data. Hysterectomy with unilateral oophorectomy was associated with an increased prevalence of elevated FSH (above 20 IU/L) (adjusted odds ratio (OR) 2.4, 95% CI 1.3 4.6) compared with women who had not had a hysterectomy or oophorectomy. Among women with two ovaries, hysterectomy was associated with an increased prevalence of elevated FSH (adjusted OR 1.5, 95% CI 1.0 2.5). As a comparison of the effect size, the observed association between hysterectomy and elevated FSH is smaller than the association between FSH and current smoking (OR 2.0), a factor that is associated with a 1 2 year decrease in mean age at natural menopause. - longitudinal studies, premature ovarian failure, menopause, risk factors, sex hormones, galactose, tobacco smoke, polymorphism - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only